Up-regulation of β-catenin by a viral oncogene correlates with inhibition of the seven in absentia homolog 1 in B lymphoma cells

摘要

The protein levels of β-catenin are tightly regulated by the ubiquitin/proteasome system. We provide evidence that two distinct ubiquitin-dependent degradation pathways for β-catenin are active in the same Burkitt's lymphoma cells: Along with the classical glycogen-synthase kinase 3β-dependent destruction machinery, degradation of β-catenin through seven in absentia homolog 1 (Siah-1) ubiquitin ligase is functional in these cells. We show that inhibition of endogenous Siah-1 stabilizes and activates β-catenin in B cells. The principal Epstein-Barr virus oncoprotein, latent membrane protein 1, is involved in β-catenin up-regulation, and expression of latent membrane protein 1 in B lymphoma cells is associated with decreased Siah-1 RNA and protein levels. Thus, we demonstrate the significance of the endogenous Siah-1-dependent ubiquitin/proteasome pathway for β-catenin degradation in malignant human cells and its regulation by a viral oncogene.